Fatty Acid Oxidation 1: Study with Video Lessons, Practice Problems & Examples

Fats serve as energy storage, breaking down into glycerol and fatty acids, which convert to Acetyl CoA via beta oxidation. Fatty acids must first be activated to fatty acyl CoA, then transported into the mitochondrial matrix using the carnitine shuttle. Beta oxidation involves four steps: oxidation, hydration, further oxidation, and thiolysis, producing Acetyl CoA. Each cycle removes two carbon units, with the process repeating until the fatty acid is fully oxidized. Understanding these metabolic pathways is crucial for grasping energy production and utilization in biological systems.

Fatty Acid Oxidation 1

As we've mentioned previously, fats can be used for energy storage and they can be broken down into glycerol and fatty acids, and fatty acids can be converted into Acetyl CoA through beta oxidation. We're going to cover that process now, but before we get there, we need to talk about how fatty acids actually get into mitochondria. Before I get ahead of myself, though, I also want to mention that fats can be used for water storage as well as energy. And this comes into play more with creatures that live in desert environments, for example, camels. Most people incorrectly think that camels' humps are filled with water; they're filled with fat that the camels can convert into water. Anyhow, before we get to the fatty acids real quick, just to harken back to what we talked about in the previous unit, glycerol can be converted into DHAP which will be converted into G3P. These are substrates of glycolysis. The catabolism of glycerol yields one ATP per glycerol and 2 NADHs, which is great if you're trying to do respiration, but that's a lot of NADH to be produced, so it makes it a non-fermentable sugar. Basically, if you recall from a previous unit, it produces more NADH than the reactions can get rid of essentially making it an unsustainable sugar to use in fermentation. Anyhow, moving on to the main stuff.

Let's talk about those fatty acids. They undergo beta oxidation to enter the citric acid cycle as Acetyl CoA or, in some cases, succinyl CoA. We'll get to that later. Fatty acids have to first be activated by being converted into fatty acyl CoAs, and this reaction is not pictured here, but what you really need to know about it is that they add a CoA onto the molecule and it costs 2 ATP, sort of. I have that in quotes. Basically, it costs 1 ATP, and then you break both anhydride bonds. So, your professor likes to think of it as costing 2 ATP. Just, you know, it's in his lecture notes. That's how he thinks of it. So, in case it comes up, you know, 2 ATP but that's what the quotes are for. It's really just breaking the 2 acid anhydride bonds. This molecule, this fatty acyl CoA, will be transported into the mitochondrial matrix but it has to first be bound to carnitine. And once it's bound, it's by the way bound to carnitine by carnitine acyltransferase 1, so here is CAT1. This next step happens through this antiporter. This antiporter will pass the acyl-carnitine into the mitochondrial matrix and will move a plain carnitine out the other way. Once the acyl-carnitine gets into the matrix, it's actually going to be broken back down into acyl CoA and carnitine, and that is going to be done by carnitine acyltransferase 2, so CAT2. This enzyme right here is often called the carnitine shuttle, and it's because carnitine isn't really consumed in the process. It just kind of shuttles back and forth to move these fatty acids into the matrix where they can undergo beta oxidation. So, beta oxidation, as hopefully you figured out at this point, occurs in the mitochondrial matrix. That's why we're bringing those fatty acids in, and beta removes 2 carbon units at a time and removes them as acetyl CoA. These are being clipped off again from the fatty acyl CoA that we brought into the mitochondrial matrix. Now, basically, beta oxidation is made up of 4 repeating steps.

As you can see here in this image, well, first of all, these names are not in English but that's fine. You don't need to worry about these names. You don't really need to worry about the enzymes involved, memorizing all the specific reactions they do. So, what you should know is the basic things that are happening in each of these four steps. First, what's going on right here, this is our fatty acid. Here's our CoA. That's at least the same in whatever language this is. Actually, not sure about it. Leave a comment if you know; I'd be curious. Anyway, the CoA and the fatty acid are combined into that fatty acyl CoA right here. This is our fatty acyl CoA, and that is the activation step. Now, we have beta oxidation. Alright? So, the first thing that's going to happen is we are going to oxidize an -ane to an -ene. We're going to oxidize an -ane to an -ene, and it's an acyl CoA dehydrogenase that's going to do this. And it works basically just like succinate dehydrogenase. So, it's going to take FAD and reduce it to FADH2 in the process. And you can see really what it's doing is it's introducing a double bond right here. There is the double bond in the molecule. Alright. Now we are ready for step 2. Oh, and do take note that that double bond is between carbons 2 and 3 on this molecule, and it has a trans configuration. These are important things to note. You'll see why momentarily. Step 2, we add water to the ene to form an alcohol. And that is carried out by enoyl CoAhydratase, and it's kind of like the conversion from fumarate to malate. You can see here is our new alcohol group. Alright. Then step 3, we oxidize the alcohol. You can see there it has been oxidized to oops. I'm sorry. I circled the wrong one. There it has been oxidized to the carbonyl. And this is carried out by a beta-hydroxyacyl CoA dehydrogenase. Oh, that's a mouthful. And that's going to take NAD+ and convert it into NADH. And this is like malate dehydrogenase. So notice that there are these parallels between these particular steps we're seeing here and the reactions that we see in the citric acid cycle. These are important parallels to bear in mind. They can come up on test questions sometimes. So, the last thing that's going to happen, step 4 is thiolase is going to cleave off the acetyl CoA and add a CoA to the new end

Here’s what students ask on this topic:

What is the role of carnitine in fatty acid oxidation?

Carnitine plays a crucial role in transporting fatty acids into the mitochondrial matrix for beta oxidation. Fatty acids are first activated to fatty acyl CoA, which then binds to carnitine via carnitine acyltransferase 1 (CAT1) to form acylcarnitine. This acylcarnitine is transported into the mitochondrial matrix through an antiporter, which simultaneously moves free carnitine out. Once inside, carnitine acyltransferase 2 (CAT2) converts acylcarnitine back to fatty acyl CoA and free carnitine, allowing the fatty acyl CoA to undergo beta oxidation. This process is often referred to as the carnitine shuttle.

What are the four steps of beta oxidation?

Beta oxidation consists of four repeating steps:

1. Oxidation: Fatty acyl CoA is oxidized by acyl CoA dehydrogenase, converting FAD to FADH₂ and forming a double bond.
2. Hydration: Enoyl CoA hydratase adds water to the double bond, forming an alcohol.
3. Further Oxidation: The alcohol is oxidized by beta-hydroxyacyl CoA dehydrogenase, converting NAD⁺ to NADH and forming a carbonyl group.
4. Thiolysis: Thiolase cleaves the carbonyl group, releasing acetyl CoA and attaching a new CoA to the remaining fatty acid chain.

This cycle repeats until the entire fatty acid is converted to acetyl CoA units.

How are fatty acids activated before entering the mitochondria?

Fatty acids are activated by being converted into fatty acyl CoA. This activation involves the enzyme acyl CoA synthetase, which attaches a CoA molecule to the fatty acid. The reaction consumes 1 ATP, but since both anhydride bonds are broken, it is often considered to cost 2 ATP. The resulting fatty acyl CoA is then ready to be transported into the mitochondrial matrix via the carnitine shuttle for beta oxidation.

What happens to glycerol during fat metabolism?

During fat metabolism, glycerol is converted into dihydroxyacetone phosphate (DHAP), which is then converted into glyceraldehyde-3-phosphate (G3P). Both DHAP and G3P are intermediates in glycolysis. The catabolism of glycerol yields 1 ATP and 2 NADH per glycerol molecule. However, due to the high NADH production, glycerol is not suitable for fermentation as it produces more NADH than can be utilized, making it an unsustainable sugar for this process.

What is the significance of beta oxidation in energy production?

Beta oxidation is crucial for energy production as it breaks down fatty acids into acetyl CoA, which enters the citric acid cycle to produce ATP. Each cycle of beta oxidation removes two carbon units from the fatty acid, generating acetyl CoA, NADH, and FADH₂. These molecules are essential for the electron transport chain, where they contribute to the production of a significant amount of ATP, making beta oxidation a vital process for energy utilization in biological systems.